The CCAAT/Enhancer-Binding Protein Beta-2 Isoform (CEBPβ-2) Upregulates Galectin-7 Expression in Human Breast Cancer Cells

Abstract

Galectin-7 is considered a gene under the control of p53. However, elevated expression of galectin-7 has been reported in several forms of cancer harboring an inactive p53 pathway. This is especially true for breast cancer where galectin-7 expression is readily expressed in a high proportion in basal-like breast cancer tissues, conferring cancer cells with increased resistance to cell death and metastatic properties. These observations suggest that other transcription factors are capable of inducing galectin-7 expression. In the present work, we have examined the role of CCAAT/enhancer-binding protein beta (C/EBPβ) in inducing expression of galectin-7. C/EBP proteins have been shown to contribute to breast cancer by upregulating pro-metastatic genes. We paid particular attention to C/EBPβ-2 (also known as LAP2), the most transcriptionally active of the C/EBPβ isoforms. Our results showed that ectopic expression of C/EBPβ-2 in human breast cancer cells was sufficient to induce expression of galectin-7 at both the mRNA and protein levels. In silico analysis further revealed the presence of an established CEBP element in the galectin-7 promoter. Mutation of this binding site abolished the transcriptional activity of the galectin-7 promoter. Chromatin immunoprecipitation analysis confirmed that C/EBPβ-2 binds to the endogenous galectin-7 promoter. Analysis of galectin-7 protein expression in normal epithelia and in breast carcinoma by immunohistochemistry further showed the expression pattern of C/EBPβ closely micmicked that of galectin-7, most notably in mammary myoepithelial cells and basal-like breast cancer where galectin-7 is preferentially expressed. Taken together, our findings suggest that C/EBPβ is an important mediator of galectin-7 gene activation in breast cancer cells and highlight the different transcriptional mechanisms controlling galectin-7 in cancer cells.

EGF Up-Regulates miR-31 through the C/EBPβ Signal Cascade in Oral Carcinoma

“…This study identified faint EGFR immunoreactivity, scattered C/EBPβ immunoreactivity and sporadic miR-31 staining in non-cancerous oral mucosa, which is in agreement with our previous studies as well as those of others [1], [9], [33]. Since EGFR and miR-31 are highly expressed in OSCC tissues [2], [9], [10], in this study we were able to further clarify that there is concordance in the expression of EGFR, C/EBPβ and miR-31 in OSCC samples.…”

Towards molecular mechanisms regulating the expression of galectins in cancer cells under microenvironmental stress conditions

“…Indeed, the biological role of galectin-7 cannot be solely related to its pro-apoptotic functions due to the crosstalk between both p53 and NF-jB, as recently demonstrated in MCF7 breast cancer cells [65]. In addition, recent studies have revealed that the upregulation of galectin-7 in breast cancer cell lines MCF7 and MDA-MB-231 is driven by C/EBPb-2, which can explain the paradox of concomitant galectin-7 overexpression in cancer cells and p53 mutation [66]. It should be noted that the role of C/EBP transcription factors in cellular responses to stresses, including inflammatory and ER stresses, is well known [67].…”

Galectin-14 expression in ovarian cancer

“…Understanding the molecular mechanisms controling expression of gal-14 will also be needed to determine which pathways controls its expression in specific tumor subtypes. It is interesting to note that the promoter of lgals14 contains consensus sites for both Nf-kB, Sp-1, and c/EBP, all of which have previoulsy been shown to control expression of gal-7 in cancer cells [33,40].…”